Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios.

Previously, extremely low, nanomolar concentrations of the mitochondria-targeted plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) were shown to prolong the lifespan of male and female Drosophila melanogaster by about 10 % (Anisimov et al., Biochemistry (Moscow) 73:1329-1342, 2008). Using long-term monitoring of SkQ1 effects on the Drosophila lifespan, we analyzed different integral parameters of Drosophila survival and mortality under SkQ1 treatment. Meta-analysis was used to evaluate the average SkQ1 effect measured in terms of standard deviation. The effect appeared to be 0.25 for females and 0.18 for males, which corresponds to a low effect by Cohen's "Rules-of-Thumb". The SkQ1 effects on the Drosophila lifespan were reproducible over six years and showed no relationship to fluctuations in the mean lifespan of the w(1118) line used in the experiments, methods of preparation and administration of the drug, seasons, or calendar years. Adding SkQ1 to fly food was associated with a reduction in early mortality and a decrease in random variation in lifespan. All survival curves were fitted by Gompertz function. Analysis of the Gompertz function parametric plane demonstrated significant differences between points corresponding to experimental and control cohorts. The Strehler-Mildvan correlations for 11 experiments with females and for 7 experiments with males were calculated. The significant increase in the slope of the regression lines indicated that feeding flies SkQ1 reduced the rate of fall of fly vitality and, consequently, slowed aging. These findings indicated that the SkQ1 effect on lifespan was associated with both elevation of life quality and slowing of aging.

[The effect of volatile antioxidants of plant origin on leukemogenesis in mice].

The effect of savory essential oil added with drinking water (150 ng/ml) or with feed (2.5 microg/g) on the lifetime of AKR mice and the parameters of oxidative stress in animal blood were investigated. It was found for the first time that long-term administration of an essential oil in low doses increased the average lifetime of mice by 20-35% and was accompanied by a decrease in the hemolysis level and the content of lipid peroxidation products in erythrocytes of mice, as well as alteration in the structural state of their membranes and stabilization of polyunsaturated fatty acids level in mice liver cells.

[Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid (phenosan) on the development of malignant neoplasms].

The effect of different doses of synthetic antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl)propionic acid (phenosan) on the development of spontaneous leukemia in AKR mice was studied. The drug efficiency was determined from the survival curves, animal life spans, and the incidence of leukemia. Phenosan exhibited a pronounced antitumor activity at therapeutic (10(-4) mol/kg, 4 administrations) and ultra-low (10(-14) mol/kg, 4 administrations) doses. The dose of 10(-4) mol/kg proved most efficient to increase the life span of the shortlived subpopulation, while the dose of 10(-14) mol/kg increased the life span of the long-lived subpopulation. The ultra-low dose of the drug seems promising as a prophylactic agent.

[The differences and regularities of life-span dynamics for human and animal populations]. / Skhodstvo i razlichie v zakonomernosti smertnosti liudei i zhivotnykh.

The dynamics of mortality of several generations of man, Wistar rats and line Canton-S fruit flies Drosophila melanogaster was investigated. The result was, that the correlation between sample mean and sample variance was negative for man, positive for flies and was absent for rats. To fit the survival curve we chose two-parametric Gompertz function. Starting from Strehler-Mildwan correlation (linear correlation between Gompertz function parameters), we obtained theoretical dependence between life-span mean and variance. This dependence had complex shape and points, corresponding to different species were situated at different segments of this curve that is corresponding to the various sign of correlation between these characteristics. Increasing of the mean man life-span attribute usually to advances in medicine and social environment. Associated with this the decreasing of the life-span variance, as it follows from this paper, depends on parameter point location on parametric plane, i.e. from biological feature of species.

[Historical dynamics of life-span distribution of Man]. / Istoricheskaia dinamika raspredeleniia prodolzhitel'nosti zhizni cheloveka.

In this activity the historical dynamics of life-span distribution parameters of the people was investigated in 12 developed countries encompassing the period of 1750-1998 years, it is treated about 1200 life tables. The approximately of a linear segment of a curve of age-specific death rate by the Gompertz function allows getting an analytical view of the life-span distribution. It is shown that the decreasing of the lower age range since 35 years till 10 years a little bit augments an approximation error. The Stehler-Mildvan correlation parameters are computed for each country, for each year during all indicated period. Estimations of the average life, modal age, dispersion etc. are obtained. It draws a conclusion about the limitation and stabilization of modal age at preservation of existing regularity in dynamics of the life-span distribution parameters.

[A possible mechanism of action of biologically active substances in extra-low concentrations at cellular and subcellular levels]. / Vozmozhnyi mekhanizm deistviia sverkhmalykh kontsentratsii biologicheski aktivnykh veshchestv na kletochnom i subkletochnom urovniakh.

A model of interaction between biologically active substances and macromolecular structures is proposed. The solutions of kinetic equations of discrete and continuous cases were obtained which predict nonmonotonous dose dependences.